CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo
Fig 9
Evidence for transmission of proviral genomes from multipotent CD4+ HSPCs to differentiated peripheral blood cells.
A. Flow cytometric plots showing purity of CD4-negative lineages containing provirus identical to HSPC-derived provirus. “Pre” indicates the cell population post CD4-bead depletion and prior to fluorescence activated cell sorting (FACS). “Post” indicates the cell populations following FACS. Numbers in the upper right corner indicate the frequency of cells in that quadrant. The frequency of CD4+ cells that were also CD3+ by gating was 0% (see also Table 5). B and C. Phylogenetic trees showing genetic relationships amongst amplicons. HIV RNA shown is cell-associated (Fig 10B). Arrows indicate location of identical amplicons shown in Fig 10. Red lines indicate identical sequences. Scale indicates nucleotide substitutions per site. ACH2, 89.6, BaL, YU-2, HXB2 and NL4-3 are subtype B HIVs. 84ZR085 (84ZR) and 94UG114 (94UG) are subtype D HIV molecular clone outgroups [32]. Phylogenetic analysis was performed by maximum likelihood method using MEGA7[33] and history was inferred based on the Hasegawa-Kishino-Yano model [34]. The tree with the highest log likelihood is shown. Abbreviations: PBMC, unfractionated peripheral blood mononuclear cells; BMMC, bone marrow mononuclear cell (column flow-through).